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However, the study\u2010specific focus on individual cell types, disease models or experimental approaches has limited our ability to infer common and disease\u2010specific responses. This meta\u2010analysis integrates bulk and single\u2010cell transcriptomic datasets of microglia and monocytes from disease models of autoimmunity, neurodegeneration, sterile injury, and infection to build a comprehensive resource connecting myeloid responses across CNS disease. We demonstrate that the bulk microglial and monocyte program is highly contingent on the disease environment, challenging the notion of a universal microglial disease signature. Integration of six single\u2010cell RNA\u2010sequencing datasets revealed that these disease\u2010specific signatures are likely driven by differing proportions of unique myeloid subpopulations that were individually expanded in different disease settings. 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